Mechanisms of Cell Competition in Growth and Development

联系PD/PI：Johnston，Laura A。 这项工作解决的中心问题是细胞如何传达它们的健康和识别 异常的适应性差异，可能会危及生长中的组织。许多证据表明， 对适应性差异的认识引发了相互作用，防止较弱的细胞 为动物做出贡献，促进最佳组织和组织健康。细胞竞争是一种 促进这一动态平衡过程的机制，并在识别细胞时启动 他们更健壮的邻居认为他们不太适合。两国竞争行为的例子 不同适合度的细胞很多，但研究最多的是核糖体减少所诱导的细胞。 蛋白质(RP)，或转录因子Myc表达降低或增强。发展中的 果蝇翅膀是研究细胞竞争的关键范式--作为一个模型系统，它是 在活体动物细胞间相互作用的马赛克研究中无与伦比，并提供无与伦比的 遗传和分子工具包。我们最近发现，“赢家”之间的交流 失败者细胞是由一种新的信号通路介导的，该信号通路由增选的成分组成 来自高度保守的先天免疫反应途径。我们的长期目标是探索 既有关于细胞竞争的基本问题(这是如何工作的)，也有关于细胞竞争的最终问题(这是为了什么)。 在这个方案中，我们主要关注三个方面：1)进一步探索 信号激活被控制并仅限于附近的“失败者”细胞；2)描绘 细胞竞争在正常动物生理中的内源性作用；以及3)研究 细胞适应性感知的一般机制的存在。 第6页 项目摘要/摘要

Contact PD/PI: Johnston, Laura A. The central problem this work addresses is how cells communicate their fitness and recognize aberrant fitness differences that might endanger growing tissues. Much evidence indicates that the recognition of fitness disparities elicits interactions that prevent the weaker cells from contributing to the animal, promoting optimal tissue and organismal fitness. Cell competition is a mechanism that facilitates this homeostatic process, and is initiated upon recognition of cells perceived as less fit by their more robust neighbors. Examples of competitive behavior between cells of different fitness are numerous, but the best studied those induced by reduced ribosomal proteins (Rp), or reduced or enhanced expression of the transcription factor Myc. The developing Drosophila wing is the critical paradigm for study of cell competition - as a model system it is unsurpassed for mosaic studies of cell-cell interactions in living animals, and offers unparalleled genetic and molecular toolkits. We recently discovered that communication between the “winner” and “loser” cells is mediated by a novel signaling pathway consisting of components co-opted from the highly conserved innate immune response pathways. Our long-term goal is to explore both proximate (how does this work) and ultimate (what is it for) questions about cell competition. In this proposal, we focus on three major quests: 1), to further explore the mechanism by which signal activation is controlled and restricted to only nearby “loser” cells; 2) to delineate the endogenous role of cell competition during normal animal physiology; and 3) to investigate the existence of a general mechanism of cell fitness sensing. Page 6 Project Summary/Abstract